Dopamine - Receptors

Receptors

Dopamine binds to and activates a group of receptors called the dopamine receptors to mediate its physiological effects in the body. The dopamine receptors are a series of five G protein-coupled receptors (GPCRs), which consist of the D₁, D₂, D₃, D₄, and D₅ receptors. As GPCRs, they work by modulating the cyclic adenosine monophosphate (cAMP) second messenger system to produce a cellular response. The five receptors are individually categorized into two distinctive groups based on their varying properties and effects, the D1-like and D2-like subfamilies. The D₁ and D₅ receptors belong to the D1-like subfamily. They are coupled to G_s and increase the cellular concentrations of cAMP by the activation of the enzyme adenylate cyclase. The D₂, D₃, and D₄ receptors belong to the D2-like subfamily. They are coupled to G_i/G_o and decrease the cellular concentrations of cAMP by inhibition of adenylate cyclase. Ultimately, the cAMP second messenger system, through several downstream mechanisms, works by modulating the opening of plasmalemmal ion channels that allow positively charged ions such as Na+ and K+ to enter or exit the cytoplasm of the cell, thereby generating or inhibiting an action potential. The receptors also couple directly to ion channels via the G-proteins. The D1-like receptors have various effects on neuronal activity, while the D2-like receptors tend to decrease action potential generation and are therefore usually inhibitory.

The D₁ receptor is the most widespread dopamine receptor in the central nervous system. The D₃, D₄, and D₅ receptors are present in significantly lower levels than are the D₁ and D₂ receptors. In fact, the D₁ receptors are approximately 100x more common than the D₅ receptors. However, dopamine binds to the D₃, D₄, and D₅ receptors with nanomolar or submicromolar affinity constants, while its corresponding constants for D₁ and D₂ receptors are in the micromolar ranges. As an example, dopamine has 20-fold higher binding affinity for the D₃ receptor in comparison to the D₂ receptor, and 10-fold higher binding affinity for the D₅ receptor over the D₁ receptor. Hence, overall activation of the system seem to be more or less well-balanced.